Anti-Inflammatory Effect of Dopamine D2 Receptor Agonist Cabergoline Against L-Arginine-Induced Acute Pancreatitis in Rats.

Severe acute pancreatitis (SAP) is an inflammatory disorder of the pancreas that may extend to other organs resulting in systemic injury. Unfortunately, there is no specific treatment beyond supportive management. Therefore, the current study explores the role of cabergoline (CAB) against l-arginine (l-arg)-induced SAP and systemic injury. Thirty male, adult, Sprague-Dawley rats were arbitrarily allocated into five groups; Normal, CAB (rats received CAB [0.5 mg/kg, orally], SAP [rats were intraperitoneally injected with 50% l-arg at 250 mg/100 g, 50% w/v, pH 7.4, twice with 1 h interval]), SAP + CAB-L, and SAP + CAB-H (rats received CAB [0.1 and 0.5 mg/kg, orally, respectively, for 7 days then were injected with l-arg twice with 1 h interval]). The results indicated that CAB significantly mitigated l-arg-induced damage to the pancreas, lung, liver, and kidney as observed through histopathological examination. Oral administration of CAB (0.5 mg/kg) significantly reduced the serum activities of amylase, lipase, ALT, AST, and the level of creatinine (p < 0.001), and ameliorated pancreatic oxidative stress marked by pancreatic levels of MDA and GSH (p < 0.001), compared to the SAP group. Moreover, CAB (0.5 mg/kg) significantly reduced inflammation as indicated by reduced levels of TNF-α, IL-6, -1β, and NLRP3 (p < 0.001, 0.001, 0.01, and 0.001, respectively). Additionally, CAB reduced the levels of TLR4, NF-κB, NLRP3, and caspase-1 in the pancreatic tissues upon comparison with the SAP group. In conclusion, CAB could offer a new avenue for the prevention of SAP and systemic inflammation mitigation.